The Testicular Iron Shuttle: A "Nurse" Function of the Sertoli Cells (original) (raw)
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The Sertoli cell: one hundred fifty years of beauty and plasticity
SUMMARY It has been one and a half centuries since Enrico Sertoli published the seminal discovery of the testicular 'nurse cell', not only a key cell in the testis, but indeed one of the most amazing cells in the vertebrate body. In this review, we begin by examining the three phases of morphological research that have occurred in the study of Sertoli cells, because microscopic anatomy was essentially the only scientific discipline available for about the first 75 years after the discovery. Biochemistry and molecular biology then changed all of biological sciences, including our understanding of the functions of Sertoli cells. Immunology and stem cell biology were not even topics of science in 1865, but they have now become major issues in our appreciation of Sertoli cell's role in spermatogenesis. We end with the universal importance and plasticity of function by comparing Sertoli cells in fish, amphibians, and mammals. In these various classes of vertebrates, Sertoli cells have quite different modes of proliferation and epithelial maintenance, cystic vs. tubular formation, yet accomplish essentially the same function but in strikingly different ways.
Enrico Sertoli and the supporting cells of the testis “Morphology is function”
Pathologica, 2019
In 1865, Enrico Sertoli, at the age of 23, published an article in his own name entitled: "About the existence of special branched cells in the seminiferous tubules of the human testis". These were Sertoli's ideal cells; in this paper he arrived at a perspicacious description of the morphology and function of these cells and in the subsequent articles he investigated the topic of spermatogenesis. Despite the importance of Sertoli's discovery, the attention of the scientific literature remained very limited after Sertoli's death for half a century and the partial eclipse finished only in the 1970s of the twentieth century. "Il testicolo dell'uomo è costituito, come ognun sa, nella sua parte più essenziale, da un numero stragrande di piccoli canaletti, tortuosi e tra loro aggomitolati, che terminando nella loro estremità a fondo cieco oppure ad anse, a due e tre superiormente si uniscono in unici canaletti non tortuosi" Enrico Sertoli,
50 years of spermatogenesis: Sertoli cells and their interactions with germ cells
Biology of Reproduction, 2018
The complex morphology of the Sertoli cells and their interactions with germ cells has been a focus of investigators since they were first described by Enrico Sertoli. In the past 50 years, information on Sertoli cells has transcended morphology alone to become increasingly more focused on molecular questions. The goal of investigators has been to understand the role of the Sertoli cells in spermatogenesis and to apply that information to problems relating to male fertility. Sertoli cells are unique in that they are a nondividing cell population that is active for the reproductive lifetime of the animal and cyclically change morphology and gene expression. The numerous and distinctive junctional complexes and membrane specializations made by Sertoli cells provide a scaffold and environment for germ cell development. The increased focus of investigators on the molecular components and putative functions of testicular cells has resulted primarily from procedures that isolate specific ...
Reproduction, 2003
Disorders of testicular function may have their origins in fetal or early life as a result of abnormal development or proliferation of Sertoli cells. Failure of Sertoli cells to mature, with consequent inability to express functions capable of supporting spermatogenesis, is a prime example. In a similar way, failure of Sertoli cells to proliferate normally at the appropriate period in life will result in reduced production of spermatozoa in adulthood. This review focuses on the control of proliferation of Sertoli cells and functional maturation, and is motivated by concerns about 'testicular dysgenesis syndrome' in humans, a collection of common disorders (testicular germ-cell cancer, cryptorchidism, hypospadias and low sperm counts) which are hypothesized to have a common origin in fetal life and to reflect abnormal function of Sertoli (and Leydig) cells. The timing of proliferation of Sertoli cells in different species is reviewed, and the factors that govern the conversion of an immature, proliferating Sertoli cell to a mature, non-proliferating cell are discussed. Protein markers of maturity and immaturity of Sertoli cells in various species are reviewed and their usefulness in studies of human testicular pathology are discussed. These markers include anti-Mullerian hormone, aromatase, cytokeratin-18, GATA-1, laminin alpha5, M2A antigen, p27 kip1 , sulphated glycoprotein 2, androgen receptor and Wilms' tumour gene. A scheme is presented for characterization of Sertoli-cell only tubules in the adult testis according to whether or not there is inherent failure of maturation of Sertoli cells or in which the Sertoli cells have matured but there is absence, or acquired loss, of germ cells. Functional 'de-differentiation' of Sertoli cells is considered. It is concluded that there is considerable evidence to indicate that disorders of maturation of Sertoli cells may be a common underlying cause of human male reproductive disorders that manifest at various life stages. This recognition emphasizes the important role that animal models must play to enable identification of the mechanisms via which failure of proliferation and maturation of Sertoli cells can arise, as this failure probably occurs in fetal life.
History of the Sertoli Cell Discovery
The first edition of The Sertoli Cell was an appropri- ate vision of the late Professor Lonnie D. Russell, because he studied the Sertoli cell in more depth than most other modern-day scientists. He published more than 200 papers, of which nearly half were focused on the Sertoli cell, including the first book devoted to the cell, which he coedited with Michael D. Griswold [1]. Therefore, this chapter is written in honor of Lonnie because he was a fun-loving friend and visionary scientist who always used the microscope and his imagination to find new insights into complex scien- tific problems of the testis, and in particular the Sertoli cell. Lonnie’s devotion to this cell was exemplified by the license plate that he attached to his automo- bile, which read “Sertol 1,” and by his cat whose name was also “Sertoli.” Factual events surrounding Sertoli’s life were gathered from reading numerous reviews [2–9], particularly those of the distinguished scholar Brian P. Setchell [10,11], whose foreword in the first book provided a sincere and deserved admirable look at Enrico Sertoli [12].
Sertoli Cells: Architects of Male Reproductive Function and Clinical Impacts
Akunna G.G., Abah E.D. & Saalu L.C (2024). Sertoli Cells: Architects of Male Reproductive Functions and Clinical Impacts, 2023
The male testes are essential for sperm production and hormone regulation, with Sertoli cells as the unsung heroes orchestrating these processes. This review explores the world of Sertoli cells, discussing their structure, functions, and critical role in spermatogenesis. Named after Enrico Sertoli, these cells are pivotal within seminiferous tubules, forming the blood-testis barrier and providing support to developing germ cells. They also play a vital role in hormone regulation, fetal testis development, and various clinical conditions, including testicular tumors, male infertility, and androgen insensitivity syndrome. Understanding the intricate web of Sertoli cell biology not only enhances our comprehension of male reproductive health but also lays the groundwork for innovative diagnostic and therapeutic approaches in the fields of andrology and endocrinology.
Sertoli cells (SCs) play a crucial role in testis differentiation, development and function, determining the magnitude of sperm production in sexually mature animals. For over 40 years, it has been considered that these key testis somatic cells stop dividing during early pre-pubertal phase, between around 10 to 20 days after birth respectively in mice and rats, being after that under physiological conditions a stable and terminally differentiated population. However, evidences from the literature are challenging this dogma. In the present study, using several important functional markers (Ki-67, BrdU, p27, GATA-4, Androgen Receptor), we investigated the SC differentiation status in 36 days old and adult Wistar rats, focusing mainly in the transition region (TR) between the seminiferous tubules (ST) and the rete testis. Our results showed that SCs in TR remain undifferentiated for a longer period and, although at a lesser degree, even in adult rats proliferating SCs were observed in this region. Therefore, these findings suggest that, different from the other ST regions investigated, SCs residing in the TR exhibit a distinct functional phenotype. These undifferentiated SCs may compose a subpopulation of SC progenitors that reside in a specific microenvironment capable of growing the ST length if needed from this particular testis region. Moreover, our findings demonstrate an important aspect of testis function in mammals and opens new venues for other experimental approaches to the investigation of SC physiology, spermatogenesis progression and testis growth. Besides that, the TR may represent an important site for pathophysiological investigations and cellular interactions in the testis.
The Sertoli cell received its family name in a paper published by von Ebner [1] in which he described the cells as “the cells of Sertoli.” It is amazing that the early scientists were able to deduce the cell’s basic structure so well, especially when consideration is given to the poor resolution of microscopes in the 1800s (see Chapter 1) and the lack of proper fixation, embedding, sectioning, and staining. In fact, Sertoli’s original observations were so intuitive that few scientists at that time bothered to study the cell in great depth, because most everyone accepted his descriptions and went on to other more important topics of the day. Most scientists waited for the improved resolution provided by the electron microscope before returning to the study of the Sertoli cell. From 1865, when Sertoli published his famous observations, until 1950, approximately 85 manuscripts were published with Sertoli cell or other descriptive names for this cell in the title or as key words. Then in 1953 the first paper to observe the testis with the transmission electron microscope was published [2]. However, it was most likely the work of Don Fawcett at Harvard in the 1950s [3, 4] that firmly established the importance of study- ing Sertoli cell morphology, because from 1951 until 1973, the year that Lonnie Russell published his first manuscript on testicular morphology [5], the number of publications dealing with the Sertoli cell jumped to approximately 440. From 1973 to 1990, about 4000 Sertoli cell papers were published, which is an indica- tion of the recognition of the importance of Sertoli cells in testicular function. Such growth in Sertoli cell inter- est is a direct result of the tremendous impact that morphological studies, especially those of Dr. Russell, have had on the reproductive sciences.